# Asymptomatic Cryptococcal Antigenemia: A Multi-clinic Cross-Sectional Study on the Prevalence, Associated Factors and Predictors of Three-Month Outcomes Among Antiretroviral-Naïve and Antiretroviral-Experienced HIV Patients in Dar es Salaam, Tanzania

## TL;DR

This study found that asymptomatic cryptococcal antigenemia is more common in HIV patients not on antiretroviral therapy and is linked to worse outcomes.

## Contribution

The study provides new insights into ACA prevalence and outcomes in both ART-naïve and ART-experienced HIV patients in Tanzania.

## Key findings

- The overall ACA prevalence was 4.8%, higher in ART-naïve patients (8.1%) than ART-experienced (2.5%).
- CrAg-positive patients had a 69% likelihood of adverse outcomes like meningitis or death within three months.
- Headache and recent hospitalization were significantly associated with CrAg positivity.

## Abstract

Background: Cryptococcal meningitis remains a leading cause of HIV/AIDS-related mortality, predominantly in Sub-Saharan Africa. Current screening and prevention efforts primarily target antiretroviral therapy (ART)-naïve patients, whereas strategies for ART-experienced individuals are less well defined.

Objectives: This study primarily aimed at determining the prevalence of asymptomatic cryptococcal antigenemia (ACA) among ART-naïve and ART-experienced patients, along with associated factors and predictors of three-month outcomes among HIV patients in three HIV clinics in Dar es Salaam, Tanzania. Secondarily, factors associated with serum cryptococcal antigen positivity in the overall study population were also assessed.

Methods: This cross-sectional clinic-based study recruited 273 HIV-positive participants (ART-naïve and ART-experienced), attending three HIV care clinics in Dar es Salaam over a period of three months. A convenient sampling technique was employed, and all eligible participants were recruited until the desired sample size was reached. The study included adults (≥18 years) with recent CD4 cell counts of ≤200 cells/μL and ART-experienced patients (on ART treatment for more than six months) who had a viral load ≥1000 copies/mL. Individuals with symptoms of meningitis and recent fluconazole use were excluded. Screening for serum cryptococcal antigen (CrAg) was performed in all participants. The predetermined three-month outcomes, including development of meningitis, hospitalization, and mortality, were assessed.

Results: The overall prevalence of ACA was 4.8% (13/273; 95% CI: 2.6-8.0). Among ART-experienced patients, the prevalence was 2.5% (4/162; 95% CI: 0.7-6.2), compared to 8.1% (9/111; 95% CI: 3.8-14.8) in the ART-naïve patients (p < 0.05). At three months, the likelihood of death, development of cryptococcal meningitis, or hospitalization was significantly higher among CrAg-positive patients (69%) compared to CrAg-negative patients (p < 0.05). Overall, a history of headache within the preceding two weeks and hospitalization in the past 12 months were significantly associated with CrAg positivity.

Conclusion: The overall prevalence of ACA across the three HIV clinics in Dar es Salaam was 4.8%, with lower prevalence observed among ART-experienced patients compared to ART-naïve individuals. CrAg positivity was a strong predictor of adverse outcomes at three months in both populations. These findings underscore the need for more robust, risk-based guidelines on screening and surveillance even among ART-experienced patients.